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Eckhardt C.L.,Emma Childrens Hospital | Van Velzen A.S.,Emma Childrens Hospital | Peters M.,Emma Childrens Hospital | Astermark J.,Skåne University Hospital | And 42 more authors.
Blood | Year: 2013

Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 non-severe hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A. ( Blood . 2013; 122(11):1954-1962) © 2013 by The American Society of Hematology.


PubMed | Aghia Sofia Childrens Hospital, University of Crete, Hippokrateion Hospital, P & A Kuriakou Childrens Hospital and National and Kapodistrian University of Athens
Type: | Journal: Journal of paediatrics and child health | Year: 2017

To describe children with pertussis who required intensive care.This is a retrospective analysis of pertussis admissions to all (six) national intensive care units in Greece from 2003 to 2013.A total of 31 children were included, 28 of whom were younger than 12months old. Cough was the most prominent symptom, being present in 27 of 31 (87%) patients, and on admission, only 7 (22.6%) satisfied the case definition. Mechanical ventilation was initiated in 13 (42%) patients. Six patients died because of respiratory failure (two) or multi-organ system failure (four). The patients who died had significantly higher white blood cell counts (WBC) (77800-31600, P=0.031) and neutrophils (29016-12795, P=0021) than those who survived and lower minimum values of serum sodium (125-133, P=0002). They also had a longer duration of hospitalisation prior to their paediatric intensive care unit admission (6-1days, P=0022). Three patients were diagnosed with pulmonary hypertension, and only one of them survived. Age, gender and immunisation status did not differ between survivors and non-survivors. Two patients received exchange blood transfusion, and survival benefit was not apparent.Young infants are at risk of severe pertussis, resulting in serious complications or death. Elevated WBC and low serum sodium are associated with higher mortality. Despite advances in life support and treatment of organ failure in childhood critical illness, pertussis still has substantial mortality.


Mavragani C.P.,National and Kapodistrian University of Athens | Fragoulis G.E.,National and Kapodistrian University of Athens | Rontogianni D.,Evangelismos General Hospital | Kanariou M.,Aghia Sofia Childrens Hospital | Moutsopoulos H.M.,National and Kapodistrian University of Athens
Arthritis Care and Research | Year: 2014

Objective To determine IgG4 levels in a cohort of consecutive patients with primary Sjögren's syndrome (SS) and other autoimmune diseases and explore whether they associate with distinct clinical, serologic, and histopathologic features. Methods Serum IgG4 levels were measured in 133 primary SS patients and 49 healthy donors (HDs). Seventy-four lupus and 54 rheumatoid arthritis (RA) patients served as disease controls. Immunohistochemical IgG4 analysis was performed in paraffin-embedded minor salivary gland (MSG) tissues. Results Raised IgG4 serum levels (>135 mg/dl) were detected in 10 (7.5%) of 133 primary SS patients (high-IgG4 group), in 8 (10.8%) of 74 lupus patients, in 7 (12.9%) of 54 RA patients, and in 1 (2%) of 49 HDs. Compared to the normal-IgG4 (<135 mg/dl) primary SS group, high-IgG4 patients exhibited increased prevalence of IgG4-related features (autoimmune cholangitis, autoimmune pancreatitis, and interstitial nephritis), lower rates of antinuclear antibody positivity, and higher IgG2 and IgE levels. Positive staining for IgG4+ plasma cells with an IgG4:IgG ratio ≥40% was detected in 3 of 6 available MSG tissues in the high-IgG4 group. Criteria of possible or definite IgG4-related disease (IgG4-RD) were fulfilled by 10 (7.5%) of 133 of our primary SS cohort. Conclusion Raised IgG4 serum levels were detected in 7.5% of primary SS patients in association with IgG4RD-reminiscent clinical, serologic, and histopathologic features. Whether this high-IgG4 primary SS group represents a misclassified IgG4-RD group or a distinct primary SS subtype remains to be further explored in future studies. © 2014, American College of Rheumatology.


Sklavou R.,Aghia Sofia Childrens Hospital | Karavanaki K.,National and Kapodistrian University of Athens | Critselis E.,National and Kapodistrian University of Athens | Kossiva L.,National and Kapodistrian University of Athens | And 8 more authors.
Clinical Biochemistry | Year: 2012

Objective: To evaluate the correlation of serum CRP with clinical and laboratory parameters proven to be related to the cause of infection in pediatric cancer patients. Methods: We studied prospectively for a 12-month period, 37 pediatric cancer patients, who presented with 70 episodes of febrile illness (38 bacterial and 13 viral infections). At fever's onset and 48. h later, infection indices, such as CRP, WBC, ANC were measured in the peripheral blood. Moreover we calculated the change rate of CRP over 48. h [CRP/t = (CRP48h - initial CRP)/t (t = 2 days)]. Cultures of biological fluids, PCR and antibody detection of infectious agents were also obtained. Results: When comparing patients with viral vs. bacterial infections, mean CRP levels on admission (11.0 vs. 33.1 mg/L, p = 0.005) and at 48. h (13.4 vs. 71.9 mg/L, p = 0.0007), and CRP/t (0.9 vs. 18.8 mg/L/day, p = 0.030) were significantly lower in the group with viral infection. At 48. h - follow-up, patients with positive culture had higher CRP levels (57.3 vs. 43.3 mg/L, p = 0.048) and higher CRP/t (15.9 vs. 7.7 mg/L/day, p = 0.025), compared to those without proven infection. CRP/t at 48. h was correlated with both the fever duration (r = 0.27, p = 0.027) and maximum temperature (Tmax) during the febrile episode (r = 0.30, p = 0.013). Conclusions: Single CRP values on fever initiation can differentiate between viral and bacterial infections in febrile pediatric cancer patients. Moreover the change rate of CRP over time (CRP/t) is offered as a prognostic index of bacterial infection and a marker of the total duration of fever and Tmax. © 2012 The Canadian Society of Clinical Chemists.


Goussetis E.,Aghia Sofia Childrens Hospital | Konialis C.P.,Diagnostic Genetic Center | Peristeri I.,Aghia Sofia Childrens Hospital | Kitra V.,Aghia Sofia Childrens Hospital | And 11 more authors.
Biology of Blood and Marrow Transplantation | Year: 2010

We report 2 children with X-linked chronic granulomatous disease (X-CGD) who underwent hematopoietic stem cell transplantation (HSCT) using grafts from their siblings selected before implantation to be both unaffected and HLA-matched donors. Preimplantation genetic diagnosis (PGD) along with HLA-typing were performed on preimplantation embryos by single-cell multiplex polymerase chain reaction using informative short tandem repeat markers in the HLA locus together with the gene region containing the mutations. Two singleton pregnancies resulted from the intrauterine transfer of selected embryos; these developed to term, producing 1 healthy female and 1 X-CGD carrier female, which are HLA-identical siblings to the 2 affected children. Combined grafts of umbilical cord blood (UCB) and bone marrow (BM) stem cells were administered to the recipients after myeloablative (MA) conditioning at the ages of 4.5 years and 4 years, respectively. Both patients are well, with complete donor hematopoietic and immunologic reconstitution, at 18 and 13 months posttransplantation, respectively. This report demonstrates that HSCT with HLA-matched sibling donors created by PGD/HLA typing of in vitro fertilized embryos is a realistic therapeutic option and should be presented as such to families with children who require a non-urgent HSCT but lack an HLA-genoidentical donor. © 2010 American Society for Blood and Marrow Transplantation.


Megremis S.,National and Kapodistrian University of Athens | Mitsioni A.,P And A Kyriakou Childrens Hospital | Fylaktou I.,National and Kapodistrian University of Athens | Tzeli S.K.,National and Kapodistrian University of Athens | And 4 more authors.
European Journal of Pediatrics | Year: 2011

Mutations in the Wilms' tumor suppressor gene 1 (WT1), most commonly within exons 8 or 9 or intron 9, are found in cases with the overlapping conditions of Denys-Drash and Frasier syndromes, as well as in patients with steroid-resistant nephrotic syndrome (SRNS). This study investigated the presence of WT1 gene mutations in cases with childhood SRNS, along with an evaluation of their clinical outcome. Twenty-seven Greek children with sporadic (19 cases) and familial (8 cases) SRNS were tested. Four phenotypically female patients with sporadic SRNS were found to carry de novo WT1 mutations, including two cases with p.R394W, and one case each with p.R366H, or n.1228+5G>A. Karyotype analysis found 46XX in three cases, but 46XY in one. No phenotype-genotype correlations were apparent in the WT1 gene positive cases since their clinical presentation varied broadly. Interestingly, one patient with a pathological WT1 nucleotide variation responded fully to combined therapy with cyclosporine A and corticosteroids. This study further illustrates that investigation of WT1 gene mutations is clinically useful to support definitive diagnosis in children presenting with SRNS in order to direct the most appropriate clinical management. © 2011 Springer-Verlag.


Alexopoulou E.,National and Kapodistrian University of Athens | Xenophontos P.E.,National and Kapodistrian University of Athens | Economopoulos N.,National and Kapodistrian University of Athens | Spyridopoulos T.N.,National and Kapodistrian University of Athens | And 5 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2012

Objectives: The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)-type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand. Methods: Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross-sectionally related to the MRCP-based diagnosis. Results: Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC-type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less-consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD. Conclusions: The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC-type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability. © 2012 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.


Douzgou S.,Aghia Sofia Childrens Hospital | Samples J.R.,Rocky Vista University | Samples J.R.,Oregon Health And Science University | Georgoudi N.,Institute of Child Health | Petersen M.B.,Aghia Sofia Childrens Hospital
American Journal of Medical Genetics, Part A | Year: 2011

A high frequency of the Cohen syndrome has been observed in a Greek island with 2,000 inhabitants and a high degree of inbreeding. All patients were homozygous for a COH1, exon 6-16 deletion suggesting a founder effect. We present the results of their first systematic ophthalmologic assessment. Myopia and chorioretinal atrophy were present in all patients of this cohort. Yet, in contrast to all groups previously reported, the majority presented with corneal changes, independently from age, gender, and family history. A pair of sisters, aged 11 and 15 years old, presented with bilateral keratoconus. More frequently (86%) than in any other ethnic group, Greek patients had cataracts that were bilateral and often graded as high as 3, even at a young age. As a whole, the ophthalmic phenotype of the Greek isolate of Cohen syndrome is characterized by the involvement of both the posterior and the anterior eye segment, bilaterally, in the majority of cases (93%). Greek Cohen patients that share a founder mutation are at a higher risk of developing blindness in respect to those of other ethnicities and genotypes. This study highlighted the need for pachymetry measurement as a means of surveillance and prediction of the visual impairment frequently observed. © 2011 Wiley-Liss, Inc.


PubMed | University of Rome La Sapienza, University of Rome Tor Vergata and Aghia Sofia Childrens Hospital
Type: | Journal: Skeletal radiology | Year: 2016

Multiple non-ossifying fibromas (MNOFs) occur either isolated or in association with other anomalies, are usually localized in the long bones of the lower limbs, may be radiographically confused with other skeletal lesions, and tend to heal spontaneously with the completion of the skeletal growth. Segmental distribution, either monomelic or polymelic and ipsilateral, is rare and commonly observed in the context of developmental diseases known as RASopathies, which are caused by mutations in genes that encode components or regulators within the Ras/mitogen-activated protein kinase signaling pathway. We describe here the radiographic and pathologic features of an 18-year-old Caucasian boy, whose clinical history started at the age of 3 when the diagnosis of aneurysmal bone cyst was made on a lytic lesion of his left clavicle. Over the following 2years, the patient developed polyostotic and monomelic lesions within the left humerus, radius, and ulna. No other skeletal and extra-skeletal anomalies were clinically detected. The lesions were interpreted as consistent with polyostotic fibrous dysplasia and MNOFs and showed an unusually aggressive clinical course with progressive increase in size and coalescence. The definitive diagnosis of MNOFs was made after the exclusion of fibrous dysplasia by molecular analysis. The polyostotic and monomelic distribution of the lesions and the unusually aggressive clinical course contribute to make this case of MNOFs unique.


PubMed | Aghia Sofia Childrens Hospital
Type: Journal Article | Journal: Clinical biochemistry | Year: 2012

To evaluate the correlation of serum CRP with clinical and laboratory parameters proven to be related to the cause of infection in pediatric cancer patients.We studied prospectively for a 12-month period, 37 pediatric cancer patients, who presented with 70 episodes of febrile illness (38 bacterial and 13 viral infections). At fevers onset and 48 h later, infection indices, such as CRP, WBC, ANC were measured in the peripheral blood. Moreover we calculated the change rate of CRP over 48 h [CRP/t=(CRP48h-initial CRP)/t (t=2 days)]. Cultures of biological fluids, PCR and antibody detection of infectious agents were also obtained.When comparing patients with viral vs. bacterial infections, mean CRP levels on admission (11.0 vs. 33.1mg/L, p=0.005) and at 48 h (13.4 vs. 71.9 mg/L, p=0.0007), and CRP/t (0.9 vs. 18.8 mg/L/day, p=0.030) were significantly lower in the group with viral infection. At 48 h - follow-up, patients with positive culture had higher CRP levels (57.3 vs. 43.3mg/L, p=0.048) and higher CRP/t (15.9 vs. 7.7 mg/L/day, p=0.025), compared to those without proven infection. CRP/t at 48 h was correlated with both the fever duration (r=0.27, p=0.027) and maximum temperature (Tmax) during the febrile episode (r=0.30, p=0.013).Single CRP values on fever initiation can differentiate between viral and bacterial infections in febrile pediatric cancer patients. Moreover the change rate of CRP over time (CRP/t) is offered as a prognostic index of bacterial infection and a marker of the total duration of fever and Tmax.

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